Nuclear magnetic resonance imaging (MRI) is now a major diagnostic tool. However it is still used primarily in a qualitative fashion. We believe that a thorough and potentially quantitative understanding of signal changes observed in clinical MRI requires knowledge of how the basic building blocks of tissues behave, i.e. single cells. It is only recently that nuclear magnetic resonance (NMR) microimaging has enabled the direct examination of large single cells. Using NMR microscopy the water T1, T2 and apparent diffusion coefficient (ADC) will be measured in the cytoplasmic and nuclear compartments of perfused single neurons as a function of hyper and hypotonicity and correlated with changes in cell and nuclear volume measured using confocal microscopy. To provide an extracellular compartment and a closer link to in vivo animal brain tissue, similar measurements will be performed on perfused hippocampal brain slices and the relationship between the NMR characteristics of the tissues and the cellular volume changes determined. Taken together, these data will be used to develop a realistic mathematical model of tissues. Additionally we will begin preliminary studies examining the effects of a variety of perturbations on single cells and brain slices. We believe that a thorough understanding of the signal characteristics of single cells and brain slices will lead to an improved understanding of the signal changes observed in MRI, which in turn may help develop a more quantitative approach to clinical MRI. This in turn will greatly improve the diagnostic sensitivity and specificity of MRI.